ABSTRACT The prevention of Alzheimer?s disease (AD) and cognitive decline in our aging population is a major public health priority. The older Black population is growing at a rapid pace and a significant body of evidence suggests that they suffer a greater burden of cognitive impairment and dementia compared to older Whites. Studies which collect brain tissue from well-characterized older Blacks with sufficient cognitive follow-up and risk factors are crucial to advance our understanding of the pathologic substrates underlying AD in older Blacks. In prior funding periods, the Minority Aging Research Study (MARS) made considerable progress identifying risk factors for cognitive decline in older Blacks. We enrolled a large cohort of well-characterized persons, followed them annually, and reported social, psychological, and medical risk factors related to cognitive decline, many of which appear to increase the burden of impairment compared with Whites. We also obtained autopsy from a subsample of participants who agreed to brain donation. The overall goal of the proposed continuation is to address gaps in the understanding of racial differences in the relation of risk factors and the pathologic substrates of incident AD and late-life cognitive decline. Leveraging ten years of data collection on risk factors, cognitive and motor function, a unique source of brain tissue, and donated data on Whites from ongoing studies at Rush, we propose to continue collecting clinical and postmortem data on MARS participants, test whether motor function may serve as a new biomarker for AD, and quantify new histopathologic and postmortem brain MRI indices to measure the impact of cerebrovascular pathologies in Blacks who come to autopsy. Aim 1 will examine racial differences in the association of demographic, lifestyle, and motor risk factors with incident AD. Aim 2 will examine nonlinear change in cognition and test hypotheses regarding racial differences in the effects of risk factors on changes in slope before and after incident AD. Aim 3 will evaluate racial differences in change in mobility and the associations of mobility with incident AD. Finally, Aim 4 will obtain more extensive data on cerebrovascular disease pathologies and postmortem brain MRI indices to determine the relation of brain indices to cognitive and motor function in Blacks, and compare the burden of cerebrovascular pathologies in Blacks and Whites. The proposed study provides a unique opportunity to answer critical questions about a large understudied segment of our aging society.